Cytokine-Stimulated Human Dermal Microvascular Endothelial Cells Produce Interleukin6 - Inhibition by Hydrocortisone, Dexamethasone, and Calcitriol

The effects of lipopolysaccharide (LPS), recombinant human tumor necrosis factor-α (TNF), recombinant human interleukin 1-beta (IL-1β), and interferon-γ (IFN-γ) on IL-6 production were determined by enzyme-linked immunosorbent assay (ELISA) and by Northern blot analysis in cultured human dermal microvascular endothelial cells (HDMEC). Unstimulated HDMEC did not produce significant amounts of IL-6, whereas lipopolysaccharide (LPS), TNF, and IL-1β were potent inducers of HDMEC-derived IL-6 production. Treatment with IFN-γ had no effect. IL-1β stimulation resulted in pronounced IL-6 production after 4 h, followed by complete downregulation at the transcriptional level after 24h. In contrast, LPS and TNF induced prolonged stimulation of IL-6 production by HDMEC as IL-6 mRNA transcripts were still detected after 24h treatment and IL-6 protein was markedly increased at this timepoint. The effects of hydrocortisone, dexamethasone, calcitriol acitretin, and cyclosporine A on TNF- or IL-1β-induced IL 6 production by HDMEC were determined by ELISA. Both hydrocortisone and dexamethasone dose-dependently inhibited the cytokme induced IL-6 production whereas th inhibition by calcitriol was less pronounced. In contrast acitretin and cyclosporine A had no influence on cytokin -induced HDMEC IL-6 production. These result disclose dermal endothelial cells as a major source for the pro-inflammatory cytokine IL-6, involve in the regulation of inflammatory skin processes. As IL-6 seems to play a key role in the pathogenesis of psoriasis, the beneficial effects of corticosteroids and calcitriol in this disease may partly be explained by their ability to inhibit HDMEC-derived IL-6 production